PLEASANTON, Calif.--(BUSINESS WIRE)--10x Genomics, a company focused on enabling the mastery of biology by accelerating genomic discovery, today announced publication of an article in the journal Nature of a collaborative research study with researchers at the Stanford University School of Medicine. The article entitled, Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal, utilizes the 10x Genomics Single Cell 3 Solution for single-cell RNA-seq (scRNA-seq) to unravel the priming and self-renewal mechanisms of intestinal stem cells (ISCs).
The renewal and differentiation of Lgr5+ ISCs is critical to the continuous regeneration of the epithelial lining of the gut, which enables us to absorb nutrients and provides a barrier to protect us from the external environment. Disruptions in this process can lead to or worsen human intestinal disorders such as inflammatory bowel disease (IBD), gastrointestinal cancer and Celiac disease.
This carefully regulated process occurs within a stem-cell niche called the intestinal crypt, and depends on Wnt signaling, which can be turned up by Wnt and R-spondin (RSPO) ligands. The authors sought to identify the unique functional roles of Wnt and RSPO ligands for regulating Lgr5+ ISCs and the relative contributions of both ligands to in vivo Wnt signaling and stem-cell biology.
The authors were able to show using in vivo experiments that Wnt and RSPO are not redundant signals. RSPO was shown to expand stem cell number. Although Wnt was needed to maintain Lgr5+ ISCs in the presence of RSPO, Wnt was not sufficient to induce additional numbers of Lgr5+ ISCs above a certain threshold, demonstrating that RSPO, and not Wnt, establishes the set point for Lgr5+ ISC number. The authors performed single-cell RNA-seq to definitively show that the signaling contributions of Wnt and RSPO elicited distinct effects on ISCs, by fully characterizing the expression profile for each unique cellular subtype on a cell-by-cell basis upon perturbation of those signals in vivo.
By characterizing gene expression from 13,102 single cells, Yan and colleagues were able to show that Lgr5- control cells represented differentiated cell types of the small intestinal lineages, including Paneth, goblet, enteroendocrine, enterocyte, pre-enterocyte, and tuft cells. The Lgr5+ cells consisted of three cellular sub-populations, corresponding to cycling stem cells, non-cycling stem cells, and transit amplifying cells. The authors were able to further show that these three distinct sub-populations of Lgr5+ cells were each uniquely affected by perturbations in Wnt and RSPO signaling, conclusively demonstrating that Wnts are priming factors that enable stem cells to be competent by expressing RSPO receptors on their cell surface, whereas RSPOs are actual self-renewal factors that expand stem cell number.
Single-cell analysis provided conclusive evidence for the unique roles of Wnt and RSPO signaling to their respective function, either co-operatively priming Lgr5+ cells for competency, or for RSPO-mediated self-renewal. said Grace Zheng, Ph.D., research scientist at 10x Genomics. This powerfully illustrates the utility of single-cell RNA-seq to monitor discrete stem-cell states and their dynamic perturbation. To do this with any other technology would have been extremely cumbersome, if not impossible.
We are very excited about this result, and it opens up the possibility that analogous multi-tiered regulation by priming and self-renewal factors may be a generalized property of stem cells across other organ systems, either through Wnt and RSPO or functionally equivalent stem-cell niche components, said Ben Hindson, Ph.D., president, co-founder, and chief scientific officer of 10x Genomics. This could have wide reaching implications for stem-cell research and potentially yield new insight towards therapeutic applications in the future.
The lead author of the study is Kelley Yan, M.D. Ph.D., lead author of the study, formerly a postdoctoral fellow at Stanford and now an Assistant Professor of Medicine and of Genetics and Development in the Columbia Center for Human Development at Columbia University Medical Center. The senior author is Calvin Kuo, M.D. Ph.D., Professor of Medicine at Stanford.
The article entitled, Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal, can be accessed from Nature online: http://dx.doi.org/10.1038/nature22313
For more information about this research, visit the Kuo Lab at Stanford: http://kuolab.stanford.edu/index.html
About 10x Genomics
10x Genomics is changing the definition of sequencing by providing an innovative genomics platform that dramatically upgrades the capabilities of existing sequencing technologies. This is achieved through a combination of new microfluidic science, chemistry and bioinformatics. By implementing GemCode Technology within the Chromium System, researchers can now, for the first time, find new structural variants, haplotypes and other valuable genomic information with comprehensive workflows for Single Cell, V(D)J, Genome, Exome and de novo Assembly applications that incorporate their pre-existing sequencing technologies. http://www.10xGenomics.com.
Excerpt from:
Recent Study Published in Nature Unravels a Novel Pathway for ... - Business Wire (press release)
- Bristol researcher awarded Women in Cell Biology Early Career Medal 2025 - University of Bristol - December 23rd, 2024 [December 23rd, 2024]
- Simple and effective embedding model for single-cell biology built from ChatGPT - Nature.com - December 9th, 2024 [December 9th, 2024]
- Distinguished investigator brings expertise in genetics and cell biology to Texas A&M AgriLife - AgriLife Today - October 26th, 2024 [October 26th, 2024]
- Institute of Molecular and Cell Biology (IMCB) - Agency for Science, Technology and Research (A*STAR) - October 13th, 2024 [October 13th, 2024]
- Joseph Gall, father of modern cell biology, dead at 96 - Carnegie Institution for Science - September 15th, 2024 [September 15th, 2024]
- A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion - Nature.com - June 27th, 2024 [June 27th, 2024]
- Yoshihiro Yoneda Appointed President of the International Human Frontier Science Program Organization - PR Newswire - June 27th, 2024 [June 27th, 2024]
- A new way to measure ageing and disease risk with the protein aggregation clock - EurekAlert - June 18th, 2024 [June 18th, 2024]
- How Flow Cytometry Spurred Cell Biology - The Scientist - June 18th, 2024 [June 18th, 2024]
- Building Cells from the Bottom Up - The Scientist - June 18th, 2024 [June 18th, 2024]
- From Code to Creature - The Scientist - June 18th, 2024 [June 18th, 2024]
- Adding intrinsically disordered proteins to biological ageing clocks - Nature.com - May 24th, 2024 [May 24th, 2024]
- Advancing Cell Biology and Cancer Research via Cell Culture and Microscopy Imaging Techniques - Lab Manager Magazine - May 24th, 2024 [May 24th, 2024]
- Study explores how different modes of cell division evolved in close relatives of fungi and animals - News-Medical.Net - May 24th, 2024 [May 24th, 2024]
- Solving the Wnt nuclear puzzle - Nature.com - May 24th, 2024 [May 24th, 2024]
- Prof. Jay Shendure Joins Somite Therapeutics as Scientific Co-founder - BioSpace - May 24th, 2024 [May 24th, 2024]
- One essential step for a germ cell, one giant leap for the future of reproductive medicine - EurekAlert - May 24th, 2024 [May 24th, 2024]
- May: academy-medical-sciences | News and features - University of Bristol - May 24th, 2024 [May 24th, 2024]
- Universal tool for tracking cell-to-cell interactions - ASBMB Today - May 24th, 2024 [May 24th, 2024]
- Close Encounters of Skin and Nerve Cells - The Scientist - April 15th, 2024 [April 15th, 2024]
- OrthoID: Decoding Cellular Conversations with Cutting-Edge Technology - yTech - April 15th, 2024 [April 15th, 2024]
- Impact of aldehydes on DNA damage and aging - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Redefining Cell Biology: Nondestructive Genetic Insights With Raman Spectroscopy - SciTechDaily - March 29th, 2024 [March 29th, 2024]
- Scientists Unravel the Unusual Cell Biology Behind Toxic Algal Blooms - SciTechDaily - March 19th, 2024 [March 19th, 2024]
- Ancient retroviruses played a key role in the evolution of vertebrate brains - EurekAlert - February 21st, 2024 [February 21st, 2024]
- Singapore scientists uncover a crucial link between cholesterol synthesis and cancer progression - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Scientists uncover a way to "hack" neurons' internal clocks to speed up brain cell development - News-Medical.Net - February 4th, 2024 [February 4th, 2024]
- First atomic-scale 'movie' of microtubules under construction, a key process for cell division - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Small RNAs take on the big task of helping skin wounds heal better and faster with minimal scarring - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Shengjie Feng channels the powers of cryogenic electron microscopy - Newswise - January 19th, 2024 [January 19th, 2024]
- Study pinpoints breast cancer cells-of-origi - EurekAlert - January 19th, 2024 [January 19th, 2024]
- New analysis of cancer cells identifies 370 targets for smarter, personalized treatments - News-Medical.Net - January 19th, 2024 [January 19th, 2024]
- EU funding for pioneering research on the treatment of gliomas - EurekAlert - January 19th, 2024 [January 19th, 2024]
- The future of mRNA biology and AI convergence - Drug Target Review - December 22nd, 2023 [December 22nd, 2023]
- The future of artificial breast milk, according to one lab - Quartz - December 22nd, 2023 [December 22nd, 2023]
- Shedding new light on the hidden organization of the cytoplasm - News-Medical.Net - December 22nd, 2023 [December 22nd, 2023]
- Bugs that help bugs: How environmental microbes boost fruit fly reproduction - EurekAlert - December 22nd, 2023 [December 22nd, 2023]
- Cells Move in Groups Differently Than They Do When Alone - NYU Langone Health - December 14th, 2023 [December 14th, 2023]
- Cells move in groups differently than they do when alone - EurekAlert - December 14th, 2023 [December 14th, 2023]
- Seattle Hub for Synthetic Biology plans to transform cells into tiny recording devices - GeekWire - December 14th, 2023 [December 14th, 2023]
- Virginia Tech and Weizmann Institute of Science tackle cell ... - Virginia Tech - October 16th, 2023 [October 16th, 2023]
- Vast diversity of human brain cell types revealed in trove of new ... - Spectrum - Autism Research News - October 16th, 2023 [October 16th, 2023]
- Singamaneni to develop advanced protein imaging method - The ... - Washington University in St. Louis - October 16th, 2023 [October 16th, 2023]
- Researchers find certain cancers can activate 'enhancer' in the ... - University of Toronto - October 16th, 2023 [October 16th, 2023]
- 2023 Hettleman Prizes awarded to five exceptional early-career ... - UNC Research - October 16th, 2023 [October 16th, 2023]
- Faeth Therapeutics Announces National Academy of Medicine ... - BioSpace - October 16th, 2023 [October 16th, 2023]
- From Migrant Farm Worker to Duke Scientist, Everardo Macias ... - Duke University School of Medicine - October 16th, 2023 [October 16th, 2023]
- Finding the golden ticket? Cyclin T1 is required for HIV-1 latency ... - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Spermidine May Improve Egg Health and Fertility - Lifespan.io News - October 16th, 2023 [October 16th, 2023]
- Molecule discovered that grows bigger and stronger muscles - Earth.com - October 16th, 2023 [October 16th, 2023]
- SGIOY: 3 Biotech Stocks With Potential Future Gains - StockNews.com - October 16th, 2023 [October 16th, 2023]
- Association for Molecular Pathology Publishes Best Practice ... - Technology Networks - October 16th, 2023 [October 16th, 2023]
- A new cell type with links to gastric cancer steps up for its mugshot - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Programmed cell death may be 1.8 billion year - EurekAlert - October 16th, 2023 [October 16th, 2023]
- New study confirms presence of flesh-eating and illness-causing ... - Science Daily - October 16th, 2023 [October 16th, 2023]
- New Institute for Immunologic Intervention (3i) at the Hackensack ... - Hackensack Meridian Health - October 16th, 2023 [October 16th, 2023]
- Post-doctoral Fellow in Cancer Biology in the Department of ... - Times Higher Education - October 16th, 2023 [October 16th, 2023]
- Scientists uncover key enzymes involved in bacterial pathogenicity - News-Medical.Net - October 16th, 2023 [October 16th, 2023]
- B cell response after influenza vaccine in young and older adults - EurekAlert - October 16th, 2023 [October 16th, 2023]
- Post-doctoral researcher in yeast cell biology job with UNIVERSITY ... - Times Higher Education - April 8th, 2023 [April 8th, 2023]
- expert reaction to study looking at creating embryo-like structures ... - Science Media Centre - April 8th, 2023 [April 8th, 2023]
- UCF Bone Researcher Receives National Recognition - UCF - April 8th, 2023 [April 8th, 2023]
- PhenomeX to Participate in American Association of Cancer ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Inland Empire stem-cell therapy gets $2.9 million booster - UC Riverside - April 8th, 2023 [April 8th, 2023]
- New finding in roundworms upends classical thinking about animal cell differentiation - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Biology's unsolved chicken-or-egg problem: Where did life come from? - Big Think - April 8th, 2023 [April 8th, 2023]
- Azacitidine in Combination With Trametinib May Be Effective for ... - The ASCO Post - April 8th, 2023 [April 8th, 2023]
- Researchers clear the way for well-rounded view of cellular defects - Phys.org - April 8th, 2023 [April 8th, 2023]
- We were dancing around the lab cellular identity discovery has potential to impact cancer treatments - Newswise - April 8th, 2023 [April 8th, 2023]
- Environmental stressors' effect on gene expression explored in lecture - Environmental Factor Newsletter - April 8th, 2023 [April 8th, 2023]
- RNA therapy restores gene function in monkeys modeling ... - Spectrum - Autism Research News - April 8th, 2023 [April 8th, 2023]
- Traumatic brain injury interferes with immune system cells' recycling ... - Science Daily - April 8th, 2023 [April 8th, 2023]
- Lab-grown fat could give cultured meat real flavor and texture - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Researchers reveal mechanism of polarized cortex assembly in migrating cells - Phys.org - April 8th, 2023 [April 8th, 2023]
- Probing Selfish Centromeres Unveils an Evolutionary Arms Race - The Scientist - April 8th, 2023 [April 8th, 2023]
- Meet the 2023 Outstanding Graduating Students - UMaine News ... - University of Maine - April 8th, 2023 [April 8th, 2023]
- The Worlds Sexiest Fragrance Unveiled, But Its Not For You - Revyuh - April 8th, 2023 [April 8th, 2023]
- City of Hope appoints John D. Carpten, Ph.D., as director of its ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Modernized Algorithm Predicts Drug Targets for SARS-CoV-2, Other ... - GenomeWeb - April 8th, 2023 [April 8th, 2023]
- BU researcher wins $3.9 million NIH grant to develop novel therapeutic modalities for Alzheimer's - News-Medical.Net - April 8th, 2023 [April 8th, 2023]